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Authors: Adam Rutherford

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The reality of applied science in the marketplace provides the major caveat to this story. Exactly what WHO scientists were trying to avoid came to pass. The first cases of artemisinin resistance had been discovered in Myanmar in 2004, following in the footsteps of chloroquine resistance in the mid-twentieth century. Containment of the evolved parasite became the priority, but by 2012, patients with limited responses to artemisinin were recorded in Cambodia, indicating that the resistance had spread (or possibly evolved separately). With luck, the principles of component switching and circuit tweaking that characterize synthetic biology will make the road to modifying malaria treatment easier and smarter in the years to come.

In the fledgling artemisinin farming market, prices have fluctuated wildly in cycles of boom and bust. Though this instability is undesirable, part of the argument against the establishment of a synthetic production base is that it would result in the displacement of thousands of wormwood farmers, as their livelihood would be ruined by a greatly reduced cost of synthetic production. This is one of the attacks that anti-synthetic biology campaigning groups put forward, and it may have some legitimacy. In a 2012 briefing pamphlet specifically criticizing the synthetic artemisinin project, the ETC reported that artemisinin demand could be met solely with an increase in wormwood cultivation, and therefore synthetic production was not only unnecessary but would also take production control from small-holding farmers and hand it to large Western pharmaceutical corporations.

Part of this argument runs the risk of falling foul of what's known as the Luddite fallacy, the idea that technological unemployment follows technological advances, as first mechanization and then automation replace workers. It's a fallacy, at least in the long term, because if it were true, as economist Alex Tabarrok points out, “we would all be out of work because productivity has been increasing for two centuries.” At the same time, the combination of a not-for-profit enterprise to produce an affordable drug to treat millions of people must outweigh those concerns. The collaboration between Amyris, OneWorld Health, and Sanofi-Aventis bears the hallmarks of corporate responsibility. They have agreed to work on a not-for-profit basis and to limit supply to 50 percent of the full artemisinin market, which leaves some space for traditional farming. Whether this collaboration will be the benchmark of humanitarian aid enabled by synthetic biology is yet to be seen, because at the time of this writing, synthetic artemisinin has not hit the markets. If and when it does, artemisinin will be the first genuine commercial product of synthetic biology and, if successful, it will be puzzled over, studied, and followed for years.

Should or Could? The Case for Progress

Science is primarily a public endeavor, not least because it is largely funded by the public purse, but also because the benefits of noncommercial scientific research are for all. As synthetic biology emerges, it will face all of the concerns that GM has had over the short history of biotechnology, and more as it grows. One thing seems to be essential: the discussions about synthetic biology and genetic modification must happen in public, and with the public.

The calls for bans from the opponents of genetic modification and now synthetic biology are unrealistic and destructive. They are designed to foment fear derived from an ideological position, to enrage rather than engage. The eighteenth-century satirist Jonathan Swift suggested it was not possible to reason someone out of a position that they didn't reason themselves into. If resistance to new forms of biotechnology are ideological, then contesting those views with evidence is a daunting challenge. There are legitimate and serious concerns in any of the technologies described in these pages, but they demand rational, open, and informed discussions.

GM crops are in the wild and they are in our food. Another significant challenge from green campaigners is that, once out in fields, GM crops can cross-breed with traditionally manipulated crops and the unnatural genes can outcompete their more natural counterparts in the open marketplace of nature. This is a more legitimate concern, as we know that this can happen. As with the EβF wheat in Rothamsted, gene engineering in crops is frequently aimed at reducing the need for pesticides by getting the plant to produce its own. Similarly, engineering a crop to be resistant to a weed killer is potentially useful, as it means that farmers can spray their fields with an herbicide knowing that only unwanted plants will die. But so far, field experiments have produced mixed results. Some GM crops do appear to have the effect of reducing local biodiversity, with fewer wild plants and fewer insects to pollinate them. However, it is not universal. In one experiment GM maize appeared to increase biodiversity, whereas beets and rape did the opposite. That sort of result is not uncommon: biology is messy. But this should lead us to conduct
more
experiments, not to shut down or even vandalize them.

More scientists and politicians than ever are now moving toward the stance that, in order to address mammoth population growth, poverty, and incoming climate change, genetically modified crops will be utterly necessary. Sir John Beddington, the UK government's chief scientific adviser (GCSA), told the BBC in 2011 that

If there are genetically modified organisms that actually solve problems that we can't solve in other ways, and are shown to be safe from a human health point of view, and safe from an environmental point of view, and they can solve problems we can't solve otherwise, then we should use them.

The precautionary principle is carefully threaded into that statement, suggesting the necessity of GM rather than a whimsical or commercial desire to introduce these creations. There is a simple necessity underlying Beddingfield's comment: in changing environments, many of which are going to make land in poor nations less amenable to being cultivated, we need new ways for crops to be hardier in difficult ground. Breeding is slow and cumbersome, and therefore is not a realistic option in our timeframe.

For synthetic biology, its potential for use in the service of humankind and the planet puts it in a similar camp. We don't know the full effects of introducing its products out of the lab and into the wild. One of the main demands of synthetic biology antagonists is that these cells and unnatural life-forms should not be released. We have seen with GM crops the spread of their modified genes beyond the original host, though whether these have a detrimental effect is unknown. Could any of the products of synthetic biology cause havoc? The cancer assassin circuit described in chapter 9 integrates into the genome of a virus and delivers its lethal message after infecting a cancerous cell. It is designed to target only one specific type of malignant cell and performs a calculation to precisely determine its cancerous nature. If this circuit were capable of going native and joining the natural ecosystem, would there be a risk of its entering other cells and destroying them? It is unimaginable that it could, because of the very precise nature of the design of the circuit, yet it is theoretically not impossible, just tremendously improbable. We do know that genes swap in and out from microorganisms and viruses, and this can't be ruled out.

Could Synthia live beyond the lab?
Mycoplasma mycoides
is a natural pathogen, albeit a minor, nonlethal one for goats. It might be able to survive outside the lab, though Venter's team specifically wrote into its genome a chunk of code that rendered it incapable of infection, thus denying the pathogen its favored habitat. Yet the remarkable tenacity of bacteria suggests that it could gain functions upon exposure to other bacteria, as they swap their genes.

Could Amyris's artemisinin- or biofuel-producing yeast cells escape from their vats and wreak havoc on ecosystems? It is unlikely, as they, too, are optimized for purpose, not for survival. They are not in the wild, or in field tests, though their nonliving products will be.

All of these scenarios are not airtight, but after careful consideration the risks seem almost trivial, and just like with the outstanding questions in genetically modified farming, they suggest the need for more research, not less.

Knowledge Is Value Free

In 2007, an editorial in the journal
Nature
made this comment: “Many a technology has at some time or another been deemed an affront to God, but perhaps none invites the accusation as directly as synthetic biology. For the first time, God has competition.” It was written in broad support of synthetic biology, but carries a theological misunderstanding. Ever since Eve took a bite of an apple, God, if one believes in such things, has had competition. Throughout our existence we have challenged, manipulated, and forged nature to our own ends. Our influence has shaped and defined this living world, hitherto governed by Darwinian rules. With synthetic biology we have the opportunity not to supplant those rules, but to create new lives specifically for purpose. That is not a call to defeat nature, nor to trample it underfoot any more than we have already done. In less than a fraction of a heartbeat of this planet's existence, we have done more than enough to jeopardize our continued existence here. The living planet will go on cycling according to the fixed law of gravity, with or without us, Earth's most creative and destructive offspring. Yet with smart, informed scientific decisions we have the ability to fix our past errors.

In 2005, on the thirtieth anniversary of the Asilomar meeting, Paul Berg commented, “First and foremost, we gained the public's trust, for it was the very scientists who were most involved in the work and had every incentive to be left free to pursue their dream that called attention to the risks inherent in the experiments they were doing.” One-tenth of the conference attendees were journalists who were free to observe the sometimes bitter altercations and fights between scientists. It was the scientists who raised the concerns and, by arguing about them out in public, they ensured that the outcomes were cautious, progressive, and uncontroversial.

It may be that current regulations will not be sufficient in the future, but they should be addressed at that point, not preemptively in a way that could prohibit progress. If prudent vigilance is built into the structure of research funding, public engagement, and the way the research is done and applied, then the precautionary principle is foremost in the way synthetic biology proceeds. Whether this works remains to be seen, but to halt progress is to deny the potential benefit that new technologies can provide. Furthermore, increased regulation, restricted progress, and heavy monitoring drives actual research out of the hands of publicly funded scientists, because all of these things are expensive. Those levels of bureaucracy are handled comfortably by companies with commercial interests, and they are not obligated to have open dialogues with a public who funds them.

Synthetic biology is moving at such a fast pace that many scientists are bewildered by its progress. To bring the public and politicians on board is a difficult task. Yet it is essential, as it is society that makes the decision about what we should and shouldn't do. “Democratic deliberation” is the phrase used in President Obama's 2010 bioeconomy report. To this end, in the United Kingdom in 2010, major scientific funding agencies commissioned extensive research on what people know and think about synthetic biology. Key questions emerged:

What is the purpose?

Why do you want to do it?

What are you going to gain from it?

What else is it going to do?

How do you know you are right?

These are precisely the right questions any scientist should ask of any project, so in that respect this type of dialogue is working.

Yet in reflecting on the triumph of the Asilomar meeting, Paul Berg also warned that an attempt to repeat past successes would be a futile gesture: “By contrast, the issues that challenge us today are qualitatively different. They are often beset with economic self-interest and increasingly by nearly irreconcilable ethical and religious conflicts and challenges to deeply held social values. An Asilomar-type conference trying to contend with such contentious views is, I believe, doomed to acrimony and policy stagnation, neither of which advances the cause of finding a solution.”

I don't share this pessimism. I believe that scientific research should occur in the full glare of public scrutiny and that scientists should engage with publics of all levels of expertise. This way, with data out in the open, and informed public conversations about the potential benefit and the potential harm that new technologies create, we foster a society in which rational approaches to global and local problems are normalized.

There is a revolution happening and it is in our hands. Synthetic biology promises benefits for all humankind's residency on Earth and on worlds not yet explored, far too great to ignore, repress, or censor. There is youthful optimism, a remix culture of boundless creativity that believes these new technologies will help rectify the problems we face, and at least in some quarters, there is an unprecedented willingness to push that agenda.

We will face new and unforeseen challenges, some of which we have created or at least nurtured. Yet we should strive to invent technologies that are not in conflict with nature, nor subvert or exploit it, but work alongside our sophisticated living world with its four-billion-year-evolved history. Humankind's progress is born out of our attempts to explore and understand a continuously changing landscape, and live within those means. Our exploration of the workings of living things over two or three centuries has given us the power to do things that could never have happened before. We are engineering life-forms to build fuels, drugs, treatments, tools to explore our universe, and boundless new living creations that can help our world and our tenure on it. Our responsibility is not to curtail that knowledge but to use it to better ourselves and our living planet. Sometimes this gets framed as a question of whether we should do the things that we are capable of. The answer transcends either option: we must.

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